Neurons transmit information over long distances by means of a train of action potentials (spikes); while much is known about how the spike propagates, much less is known about how the spike train originates in the soma, initial segment, and dendrites. While occasional depolarizations of the cell membrane in the somatic region will lead to a spike if they cross threshold analogous to axons), additional modes of repetitive firing are seen there: the rhythmic firing mode occurs when a prolonged depolarizing current from the synapses (or an experimentally injected current) attempts to keep the membrane potential above threshold. Because of hyperpolarizing spike afterpotentials, this leads to rhythmic firing at a rate proportional to the size of the current; the neuron thus acts as a current-to-spike-frequency converter. A third mode is self-regenerative: a spike may have a depolarizing afterpotential. If large enough, it may rise through the falling threshold (near the end of the relative refractory period), setting off an extra spike. This extra spike may set off another extra spike, etc. This study investigates the origins of all three modes (occasional spike, rhythmic firing, and regenerative firing) of repetitive discharge and attempts to relate it to known neuropathophysiology. Disorders of surviving (but malfunctioning) cells, such as in chronic pain, epilepsy, and mental retardation, are usually manifested in abnormal patterns of neuronal discharge rather than silence. Epileptic neurons (best studied of the group) in humans show high-frequency burst firing patterns, strikingly similar to the patterns produced by the extra spike mode in our studies of motoneurons and pyramidal tract neurons. We are comparing these intracellular studies to extracellular studies in external cuneate nucleus and chronic epileptogenic foci. BIBLIOGRAPHIC REFERENCES: Calvin, W. H., and John D. Loeser. Doublet and burst firing patterns within dorsal column nuclei of cat and man. Experimental Neurology. 39:406-426, 1975. Calvin, W. H., H. William, and John D. Loeser. Sterotyped doublet and burst firing patterns in neurons of normal lateral cuneate nucleus: Evidence for a normal substrate for epiletic burst responses. Electroenceph. Clin. Neurophysiol. 38:546-547, 1975. (Abstracts, American EEG Society).